| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Epidemiology and Prevention |
1 Center for Cancer Prevention Research, 2 Department of Pharmaceutics, and 3 Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey
Requests for reprints: Ah-Ng Tony Kong, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Room 226, Piscataway, NJ 08854. Phone: 732-445-3831, ext. 226; Fax: 732-445-3150; E-mail: Kongt{at}rci.rutgers.edu.
Sulforaphane, a dietary isothiocyanate, possesses potent chemopreventive effects through the induction of cellular detoxifying/antioxidant enzymes via the transcription factor nuclear factor E2–related factor 2 (Nrf2). To investigate carcinogenesis mechanisms related to the regulation of Nrf2, we examined the tumor incidence and tumor numbers per mouse in Nrf2 wild-type (+/+) and Nrf2 knockout (–/–) mice. 7,12-Dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate treatments resulted in an increase in the incidence of skin tumors and tumor numbers per mouse in both genotypes; however, both indices were markedly higher in Nrf2(–/–) mice as compared with Nrf2(+/+) mice. Western blot analysis revealed that Nrf2 as well as heme oxygenase-1, a protein regulated by Nrf2 were not expressed in skin tumors from mice of either genotype, whereas expression of heme oxygenase-1 in Nrf2(+/+) mice was much higher than that in Nrf2(–/–) mice in nontumor skin samples. Next, we examined the chemopreventive efficacy of sulforaphane in mice with both genotypes. Topical application of 100 nmol of sulforaphane once a day for 14 days prior to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate applications decreased the incidence of skin tumor in the Nrf2(+/+) mice when compared with the vehicle-treated group. Importantly, there was no chemoprotective effect elicited by sulforaphane pretreatment in the Nrf2(–/–) mice group. Taken together, our results show for the first time that Nrf2(–/–) mice are more susceptible to skin tumorigenesis and that the chemopreventive effects of sulforaphane are mediated, at least in part, through Nrf2. (Cancer Res 2006; 66(16): 8293-6)
This article has been cited by other articles:
|
|
 |
|
  M. S. Yates, Q. T. Tran, P. M. Dolan, W. O. Osburn, S. Shin, C. C. McCulloch, J. B. Silkworth, K. Taguchi, M. Yamamoto, C. R. Williams, et al. Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice Carcinogenesis, June 1, 2009; 30(6): 1024 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Ambrosone and L. Tang Cruciferous Vegetable Intake and Cancer Prevention: Role of Nutrigenetics Cancer Prevention Research, April 1, 2009; 2(4): 298 - 300. [Full Text] [PDF]
|
|
|
|
|
|
O. Azarenko, T. Okouneva, K. W. Singletary, M. A. Jordan, and L. Wilson Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane Carcinogenesis, December 1, 2008; 29(12): 2360 - 2368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Colburn and T. W. Kensler Targeting Transcription Factors for Cancer Prevention--the Case of Nrf2 Cancer Prevention Research, August 1, 2008; 1(3): 153 - 155. [Full Text] [PDF]
|
|
|
|
|
|
T. O. Khor, M.-T. Huang, A. Prawan, Y. Liu, X. Hao, S. Yu, W. K. L. Cheung, J. Y. Chan, B. S. Reddy, C. S. Yang, et al. Increased Susceptibility of Nrf2 Knockout Mice to Colitis-Associated Colorectal Cancer Cancer Prevention Research, August 1, 2008; 1(3): 187 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 From the Cover: Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction PNAS, February 19, 2008; 105(7): 2325 - 2330.
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
